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Distinct H₂O₂-Scavenging System in Yersinia pseudotuberculosis: KatG and AhpC Act Together to Scavenge Endogenous Hydrogen Peroxide.

ABSTRACT: To colonize in the digestive tract of animals and humans, Yersinia pseudotuberculosis has to deal with reactive oxygen species (ROS) produced by host cells and microbiota. However, an understanding of the ROS-scavenging systems and their regulation in this bacterium remains largely elusive. In this study, we identified OxyR as the master transcriptional regulator mediating cellular responses to hydrogen peroxide (H₂O₂) in Y. pseudotuberculosis through genomics and transcriptomics analyses. OxyR activates transcription of diverse genes, especially the core members of its regulon, including those encoding catalases, peroxidases, and thiol reductases. The data also suggest that sulfur species and manganese may play a particular role in the oxidative stress response of Y. pseudotuberculosis. Among the three H₂O₂-scavenging systems in Y. pseudotuberculosis, catalase/peroxidase KatE functions as the primary scavenger for high levels of H₂O₂; NADH peroxidase alkyl hydroperoxide reductase (AhpR) and catalase KatG together are responsible for removing low levels of H₂O₂. The simultaneous loss of both AhpC (the peroxidatic component of AhpR) and KatG results in activation of OxyR. Moreover, we found that AhpC, unlike its well-characterized Escherichia coli counterpart, has little effect on protecting cells against toxicity of organic peroxides. These findings provide not only novel insights into the structural and functional diversity of bacterial H₂O₂-scavenging systems but also a basic understanding of how Y. pseudotuberculosis copes with oxidative stress.

SUBMITTER: Wan F

PROVIDER: S-EPMC8139631 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Oxidative stress response in pathogenic mycobacteria is believed to be of significance for host-pathogen interactions at various stages of infection. It also plays a role in determining the intrinsic susceptibility to isoniazid in mycobacterial species. In this work, we characterized the oxyR-ahpC and furA-katG loci in the nontuberculous pathogen Mycobacterium marinum. In contrast to Mycobacterium smegmatis and like Mycobacterium tuberculosis and Mycobacterium leprae, M. marinum was shown to possess a closely linked and divergently oriented equivalents of the regulator of peroxide stress response oxyR and its subordinate gene ahpC, encoding a homolog of alkyl hydroperoxide reductase. Purified mycobacterial OxyR was found to bind to the oxyR-ahpC promoter region from M. marinum and additional mycobacterial species. Mobility shift DNA binding analyses using OxyR binding sites from several mycobacteria and a panel of in vitro-generated mutants validated the proposed consensus mycobacterial recognition sequence. M. marinum AhpC levels detected by immunoblotting, were increased upon treatment with H2O2, in keeping with the presence of a functional OxyR and its binding site within the promoter region of ahpC. In contrast, OxyR did not bind to the sequences upstream of the katG structural gene, and katG expression did not follow the pattern seen with ahpC. Instead, a new open reading frame encoding a homolog of the ferric uptake regulator Fur was identified immediately upstream of katG in M. marinum. The furA-katG linkage and arrangement are ubiquitous in mycobacteria, suggesting the presence of additional regulators of oxidative stress response and potentially explaining the observed differences in ahpC and katG expression. Collectively, these findings broaden our understanding of oxidative stress response in mycobacteria. They also suggest that M. marinum will be useful as a model system for studying the role of oxidative stress response in mycobacterial physiology, intracellular survival, and other host-pathogen interactions associated with mycobacterial diseases.

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Distinct H₂O₂-Scavenging System in Yersinia pseudotuberculosis: KatG and AhpC Act Together to Scavenge Endogenous Hydrogen Peroxide.

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Distinct H2O2-Scavenging System in Yersinia pseudotuberculosis: KatG and AhpC Act Together to Scavenge Endogenous Hydrogen Peroxide.

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OmicsDI is part of the ELIXIR infrastructure

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Distinct H₂O₂-Scavenging System in Yersinia pseudotuberculosis: KatG and AhpC Act Together to Scavenge Endogenous Hydrogen Peroxide.